Predicting worsening heart failure hospitalizations in patients with implantable cardioverter defibrillators: Is it all about alerts? A pooled analysis of nine trials

Background and aims: To predict worsening heart failure hospitalizations (WHFH) in patients with implantable defibrillators and remote monitoring (RM), the HeartInsight algorithm (Biotronik, Berlin, Germany) calculates a heart failure (HF) score combining seven physiologic parameters: 24-hour heart rate (HR), nocturnal HR, HR variability, atrial tachyarrhythmia, ventricular extrasystoles, patient activity, and thoracic impedance. We compared temporal trends of the HF score and its components 12 weeks before a WHFH with 12-week trends in patients without WHFH, to assess whether trends indicate deteriorating HF regardless of alert status. Methods: Data from nine clinical trials were pooled, including 2,050 patients with a defibrillator capable of atrial sensing, ejection fraction ≤ 35%, NYHA class II/III, no long-standing atrial fibrillation, and 369 WHFH from 259 patients. Results: The mean HF score was higher in the WHFH group than in the no WHFH group (42.3 ± 26.1 versus 30.7 ± 20.6, p < 0.001) already at the beginning of 12 weeks. The mean HF score further increased to 51.6 ± 26.8 until WHFH (+22% versus no WHFH group, p = 0.003). As compared to the no WHFH group, the algorithm components either were already higher 12 weeks before WHFH (24 h HR, HR variability, thoracic impedance) or significantly increased until WHFH (nocturnal HR, atrial tachyarrhythmia, ventricular extrasystoles, patient activity). Conclusion: The HF score was significantly higher at, and further increased during 12 weeks before WHFH, as compared to the no WHFH group, with seven components showing different behavior and contribution. Temporal trends of HF score may serve as a quantitative estimate of HF condition and evolution prior to WHFH

Ability to remotely monitor atrial high-rate episodes using a single-chamber implantable cardioverter-defibrillator with a floating atrial sensing dipole

Aims To allow timely initiation of anticoagulation therapy for the prevention of stroke, the European guidelines on atrial fibrillation (AF) recommend remote monitoring (RM) of device-detected atrial high-rate episodes (AHREs) and progression of arrhythmia duration along pre-specified strata (6 min…&lt;1 h, 1 h…&lt;24 h, ≥ 24 h). We used the MATRIX registry data to assess the capability of a single-lead implantable cardioverter-defibrillator (ICD) with atrial sensing dipole (DX ICD system) to follow this recommendation in patients with standard indication for single-chamber ICD. Methods In 1841 DX ICD patients with daily automatic RM transmissions, electrograms of first device-detected AHREs per patient in and results each duration stratum were adjudicated, and the corresponding positive predictive values (PPVs) for the detections to be true atrial arrhythmia were calculated. Moreover, the incidence and progression of new-onset AF was assessed in 1451 patients with no AF history. A total of 610 AHREs ≥6 min were adjudicated. The PPV was 95.1% (271 of 285) for episodes 6min…&lt;1 h, 99.6% (253/254) for episodes 1 h…&lt;24 h, 100% (71/71) for episodes ≥24 h, or 97.5% for all episodes (595/ 610). The incidence of new-onset AF was 8.2% (119/1451), and in 31.1% of them (37/119), new-onset AF progressed to a higher duration stratum. Nearly 80% of new-onset AF patients had high CHA 2DS 2-VASc stroke risk, and 70% were not on anticoagulation therapy. Age was the only significant predictor of new-onset AF. Conclusion A 99.7% detection accuracy for AHRE ≥1 h in patients with DX ICD systems in combination with daily RM allows a reliable guideline-recommended screening for subclinical AF and monitoring of AF-duration progression.</p

Benchmark test and guidelines for DEER/PELDOR experiments on nitroxide-labeled biomolecules

Distance distribution information obtained by pulsed dipolar EPR spectroscopy provides an important contribution to many studies in structural biology. Increasingly, such information is used in integrative structural modeling, where it delivers unique restraints on the width of conformational ensembles. In order to ensure reliability of the structural models and of biological conclusions, we herein define quality standards for sample preparation and characterization, for measurements of distributed dipole–dipole couplings between paramagnetic labels, for conversion of the primary time-domain data into distance distributions, for interpreting these distributions, and for reporting results. These guidelines are substantiated by a multi-laboratory benchmark study and by analysis of data sets with known distance distribution ground truth. The study and the guidelines focus on proteins labeled with nitroxides and on double electron–electron resonance (DEER aka PELDOR) measurements and provide suggestions on how to proceed analogously in other cases

Benchmark test and guidelines for DEER/PELDOR experiments on nitroxide-labeled biomolecules

Distance distribution information obtained by pulsed dipolar EPR spectroscopy provides an important contribution to many studies in structural biology. Increasingly, such information is used in integrative structural modeling, where it delivers unique restraints on the width of conformational ensembles. In order to ensure reliability of the structural models and of biological conclusions, we herein define quality standards for sample preparation and characterization, for measurements of distributed dipole–dipole couplings between paramagnetic labels, for conversion of the primary time-domain data into distance distributions, for interpreting these distributions, and for reporting results. These guidelines are substantiated by a multi-laboratory benchmark study and by analysis of data sets with known distance distribution ground truth. The study and the guidelines focus on proteins labeled with nitroxides and on double electron–electron resonance (DEER aka PELDOR) measurements and provide suggestions on how to proceed analogously in other cases